The 35-site, international FOR-DMD study (Finding the Optimum Corticosteroid (CS) Regimen for Duchenne Muscular Dystrophy) has recruited 77% (1 additional subject randomized 3/1/16--too late to include in total) of the planned 225 boys. Obtaining study drugs and recruiting for this rare disease took longer than originally anticipated so this application requests that the originally awarded funds be provided for an additional four years. The goals of FOR-DMD are to determine which of the three most commonly prescribed regimens of CS (0.75 mg/kg/d prednisone; 0.9 mg/kg/d deflazacort; 0.75 mg prednisone for 10 days, then off for 10 days) has the best risk/benefit for DMD over a three year period. All boys receive standardized treatment of complications of DMD and prevention of CS side effects. The treatment of DMD is rapidly changing with multiple clinical trials of gene modification and other strategies underway or planned. All new treatments also include CS. Standardizing CS treatment is essential for interpretation of the benefit of new treatment and for long-term combination treatment. This renewal application addresses the original hypotheses that: (1) daily CS are preferable to an intermittent regiment of CS; and (2) that deflazacort is preferable to prednisone in terms of CS toxicity. This large cohort of rigorously evaluated and followed boys also provides opportunity to test the hypothesis that specific genetic (e.g. SPP1 and LTB4) or proteomic markers will identify factors that determine disease severity and complications and predict CS benefit and toxicity. This hypothesis will be tested with other funds, already obtained which have supported a repository of serum and DNA from all boys. This rigorously-standardized subset of boys with DMD followed according to clearly defined care standards will address the uncertainties regarding CS regimen and side effect prevention that have delayed universal acceptance of CS treatment for DMD with its tragic consequence of early disability and death before age 20 vs survival with corticosteroids into the 3rd and 4th decades.